We have discovered that human and bovine milk contain mitogenic factors that stimulate DNA synthesis and cell division in cultured cells. The growth promoting activity of milk is greatest early in the lactation period, in the colostrum. The specific activity of milk in stimulating DNA synthesis is 30 to 60 times greater than that of serum. The mitogens have been partially purified. They are very stable anionic polypeptides with isoelectric points between 4.4 and 4.8. Bovine colostrum will support the growth in culture of several epithelial cell lines in the absence of serum. These cells grow indefinitely, have the same growth rate as cells grown in serum, and maintain their epithelial-like properties. Our goals is to explore the use of milk-derived growth factors for the growth of cells and tissue in vitro and in vivo. The direct objective of the proposed research are: 1) to purify and characterize the human and bovine milk mitogens; 2) to identify which cells will proliferate in colostrum; 3) to compare the effect of growth media supplemented with colostrum and serum, or cellular morphology, growth rate, differentiation and phenotypic expression; 4) to identify the site of growth factor synthesis with emphasis placed on normal mammary and mammary carcinoma cells; 5) to raise antibodies to the mitogens in order to develop a radioimmunoassay, and 6) to determine in a long range study the physiological role of milk and milk-derived growth factors in the growth of bovine and human tissue in vivo and in the health, nutrition and development of the newborn.